CT or Invasive Coronary Angiography in Stable Chest Pain.

BACKGROUND: In the diagnosis of obstructive coronary artery disease (CAD), computed tomography (CT) is an accurate, noninvasive alternative to invasive coronary angiography (ICA). However, the comparative effectiveness of CT and ICA in the management of CAD to reduce the frequency of major adverse cardiovascular events is uncertain. METHODS: We conducted a pragmatic, randomized trial comparing CT with ICA as initial diagnostic imaging strategies for guiding the treatment of patients with stable chest pain who had an intermediate pretest probability of obstructive CAD and were referred for ICA at one of 26 European centers. The primary outcome was major adverse cardiovascular events (cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke) over 3.5 years. Key secondary outcomes were procedure-related complications and angina pectoris. RESULTS: Among 3561 patients (56.2% of whom were women), follow-up was complete for 3523 (98.9%). Major adverse cardiovascular events occurred in 38 of 1808 patients (2.1%) in the CT group and in 52 of 1753 (3.0%) in the ICA group (hazard ratio, 0.70; 95% confidence interval [CI], 0.46 to 1.07; P = 0.10). Major procedure-related complications occurred in 9 patients (0.5%) in the CT group and in 33 (1.9%) in the ICA group (hazard ratio, 0.26; 95% CI, 0.13 to 0.55). Angina during the final 4 weeks of follow-up was reported in 8.8% of the patients in the CT group and in 7.5% of those in the ICA group (odds ratio, 1.17; 95% CI, 0.92 to 1.48). CONCLUSIONS: Among patients referred for ICA because of stable chest pain and intermediate pretest probability of CAD, the risk of major adverse cardiovascular events was similar in the CT group and the ICA group. The frequency of major procedure-related complications was lower with an initial CT strategy. (Funded by the European Union Seventh Framework Program and others; DISCHARGE ClinicalTrials.gov number, NCT02400229.).

Patient satisfaction with coronary CT angiography versus invasive coronary angiography: results of a single-center randomized trial.

OBJECTIVE: Because there is evidence for a clinical benefit of using coronary computed tomography (CT) angiography instead of invasive coronary angiography (ICA) in patients with suspected coronary artery disease (CAD), we ascertained if patient satisfaction could represent an important barrier to implementation of coronary CT in clinical practice. MATERIALS AND METHODS: A total of 329 patients with suspected CAD and clinical indication for ICA were randomly assigned to undergo either CT or ICA for guiding treatment. Satisfaction for both groups was assessed by patient questionnaire completed twice, ≥24 h after CT or ICA, and at follow-up after a median of 3.7 years. Assessment included preparation, concern, comfort, helplessness, pain, willingness to undergo tests again, overall satisfaction, and preference. Pearson's chi-square test and Wilcoxon rank-sum test were used. RESULTS: Overall, 91% of patients undergoing CT (152/167) and 86% undergoing ICA completed assessment (140/162, p = 0.19). Patients reported being significantly better prepared for CT, less concerned about the test, and felt less helpless than during ICA (all: p < 0.001). Subjective pain (horizontal nonmarked visual analogue scale) was significantly lower for CT (6.9 ± 14.7) than for ICA (17.1 ± 22.7; p < 0.001). At follow-up, significantly more patients in the CT group reported very good satisfaction with communication of findings compared with the ICA group (p < 0.001) and 92% would recommend the institution to someone referred for the same examination. CONCLUSIONS: Results from our single-center randomized study show very good satisfaction with coronary CT compared to ICA. Thus, superior acceptance of CT should be considered in shared decision-making. CLINICAL RELEVANCE STATEMENT: This evaluation of patient satisfaction in a randomized study shows that patients' preference is in line with the clinical benefit provided by CT and also suggests to prefer a CT-first strategy in suspected coronary artery disease. KEY POINTS: • Subjective pain was significantly lower for coronary CT angiography than for invasive coronary angiography and patients felt better prepared and less concerned about CT. • Patients were overall more satisfied with coronary CT angiography than invasive coronary angiography in a randomized controlled trial. • After a median follow-up of 3.7 years, more patients in the CT group indicated very good satisfaction with the communication of findings and with the examination itself.

Combination of computed tomography angiography with coronary artery calcium score for improved diagnosis of coronary artery disease: a collaborative meta-analysis of stable chest pain patients referred for invasive coronary angiography.

OBJECTIVES: Coronary computed tomography angiography (CCTA) has higher diagnostic accuracy than coronary artery calcium (CAC) score for detecting obstructive coronary artery disease (CAD) in patients with stable chest pain, while the added diagnostic value of combining CCTA with CAC is unknown. We investigated whether combining coronary CCTA with CAC score can improve the diagnosis of obstructive CAD compared with CCTA alone. METHODS: A total of 2315 patients (858 women, 37%) aged 61.1 ± 10.2 from 29 original studies were included to build two CAD prediction models based on either CCTA alone or CCTA combined with the CAC score. CAD was defined as at least 50% coronary diameter stenosis on invasive coronary angiography. Models were built by using generalized linear mixed-effects models with a random intercept set for the original study. The two CAD prediction models were compared by the likelihood ratio test, while their diagnostic performance was compared using the area under the receiver-operating-characteristic curve (AUC). Net benefit (benefit of true positive versus harm of false positive) was assessed by decision curve analysis. RESULTS: CAD prevalence was 43.5% (1007/2315). Combining CCTA with CAC improved CAD diagnosis compared with CCTA alone (AUC: 87% [95% CI: 86 to 89%] vs. 80% [95% CI: 78 to 82%]; p < 0.001), likelihood ratio test 236.3, df: 1, p < 0.001, showing a higher net benefit across almost all threshold probabilities. CONCLUSION: Adding the CAC score to CCTA findings in patients with stable chest pain improves the diagnostic performance in detecting CAD and the net benefit compared with CCTA alone. CLINICAL RELEVANCE STATEMENT: CAC scoring CT performed before coronary CTA and included in the diagnostic model can improve obstructive CAD diagnosis, especially when CCTA is non-diagnostic. KEY POINTS: • The combination of coronary artery calcium with coronary computed tomography angiography showed significantly higher AUC (87%, 95% confidence interval [CI]: 86 to 89%) for diagnosis of coronary artery disease compared to coronary computed tomography angiography alone (80%, 95% CI: 78 to 82%, p < 0.001). • Diagnostic improvement was mostly seen in patients with non-diagnostic C. • The improvement in diagnostic performance and the net benefit was consistent across age groups, chest pain types, and genders.

Detection of relevant extracardiac findings on coronary computed tomography angiography vs. invasive coronary angiography.

OBJECTIVES: To compare the detection of relevant extracardiac findings (ECFs) on coronary computed tomography angiography (CTA) and invasive coronary angiography (ICA) and evaluate the potential clinical benefit of their detection. METHODS: This is the prespecified subanalysis of ECFs in patients presenting with a clinical indication for ICA based on atypical angina and suspected coronary artery disease (CAD) included in the prospective single-center randomized controlled Coronary Artery Disease Management (CAD-Man) study. ECFs requiring immediate therapy and/or further workup including additional imaging were defined as clinically relevant. We evaluated the scope of ECFs in 329 patients and analyzed the potential clinical benefit of their detection. RESULTS: ECFs were detected in 107 of 329 patients (32.5%; CTA: 101/167, 60.5%; ICA: 6/162, 3.7%; p < .001). Fifty-nine patients had clinically relevant ECFs (17.9%; CTA: 55/167, 32.9%; ICA: 4/162, 2.5%; p < .001). In the CTA group, ECFs potentially explained atypical chest pain in 13 of 101 patients with ECFs (12.9%). After initiation of therapy, chest pain improved in 4 (4.0%) and resolved in 7 patients (6.9%). Follow-up imaging was recommended in 33 (10.0%; CTA: 30/167, 18.0%; ICA: 3/162, 1.9%) and additional clinic consultation in 26 patients (7.9%; CTA: 25/167, 15.0%; ICA: 1/162, 0.6%). Malignancy was newly diagnosed in one patient (0.3%; CTA: 1/167, 0.6%; ICA: 0). CONCLUSIONS: In this randomized study, CTA but not ICA detected clinically relevant ECFs that may point to possible other causes of chest pain in patients without CAD. Thus, CTA might preclude the need for ICA in those patients. TRIAL REGISTRATION: NCT Unique ID: 00844220 KEY POINTS: • CTA detects ten times more clinically relevant ECFs than ICA. • Actionable clinically relevant ECFs affect patient management and therapy and may thus improve chest pain. • Detection of ECFs explaining chest pain on CTA might preclude the need for performing ICA.

Clinical Imaging Research: Higher Evidence, Global Collaboration, Improved Reporting, and Data Sharing Are the Grand Challenges.

The four grand challenges of imaging research­increasing evidence levels, enhancing global collaboration, improving research reporting quality, and sharing trial data­can be addressed, utilizing the tail wind of digital transformation, by consolidating actions of all stakeholders, with the ultimate goal of evidence-based, reproducible, generalizable, and broadly accepted results that will improve the quality and consistency of patient care.

Kidney Injury after Intravenous versus Intra-arterial Contrast Agent in Patients Suspected of Having Coronary Artery Disease: A Randomized Trial.

Background In the absence of randomized studies, it has been controversial whether the likelihood of acute kidney injury (AKI) differs between intravenous and intra-arterial contrast agent administration. Purpose To compare intravenous versus intra-arterial contrast agent administration in relationship to AKI and analyze the association between AKI and chronic kidney disease (defined as at least mildly decreased estimated glomerular filtration rates [eGFRs]). Materials and Methods This was a prospective study (ClinicalTrials.gov: NCT00844220) that involved randomizing participants with atypical chest pain and suspected coronary artery disease (CAD) between February 2009 and August 2015 to undergo coronary CT angiography with intravenous contrast agent administration or cardiac catheterization angiography with intra-arterial contrast agent administration. This prespecified secondary analysis compared AKI (serum creatinine increase of ≥ 25% or 0.5 mg/dL after 18-24 or 46-50 hours) determined by blinded investigators using absolute differences and relative risks, including two-sided 95% confidence intervals (CIs). Results A total of 320 participants (163 [50.9%] women; mean age, 60 years ± 11) were included. Baseline eGFR did not differ between the CT angiography group (84.3 mL/min/1.73 m2 ± 17.2) and the catheterization group (87.1 mL/min/1.73 m2 ± 16.7) (P = .14). AKI occurred in nine of 161 participants in the CT angiography group (5.6%; 95% CI: 3%, 10%) and in 21 of 159 participants in the catheterization group (13.2%; 95% CI: 9%,19%) (relative risk, 2.4; 95% CI: 1.1, 5.0; P = .02). Also in the subgroup of participants without obstructive CAD, in those not requiring coronary interventions, AKI was more common in the catheterization group (11.9%; 95% CI: 8%, 19%) than in the CT angiography group (4.3% [95% CI: 2%, 9%]; difference, 7.7% [95% CI: 1.3%, 14.1%]; relative risk, 2.8 [95% CI: 1.1, 7.0]; P = .02). Obstructive CAD (odds ratio [OR]: 2.7 [95% CI: 1.1, 6.6]; P = .02), femoral catheter access (OR: 2.5 [95% CI: 1.1, 5.6]; P = .04), and cine ventriculography were associated with AKI (OR: 2.3 [95% CI: 1.0, 4.9]; P = .03). In multivariable analysis, the presence of postcontrast AKI was associated with chronic kidney disease (hazard ratio: 12.4 [95% CI: 4.5, 34.6]; P < .01). Conclusion Acute kidney injury was more common after cardiac catheterization than after CT angiography in this prospective randomized study of patients suspected of having coronary artery disease. © RSNA, 2019 Online supplemental material is available for this article. See also the editorial by Einstein and Newhouse in this issue.

Clinical trials in radiology and data sharing: results from a survey of the European Society of Radiology (ESR) research committee.

OBJECTIVES: To determine the current situation and future directions of clinical trials and data sharing in radiology. METHODS: This survey was conducted between July and September 2018 among European heads of imaging departments and speakers at the Clinical Trials in Radiology sessions at ECR 2015-2018. The survey was approved by the ESR research committee, was administered online, and chi-square tests were used. RESULTS: The overall response rate was 29% (132/460). Responses were received from institutions in 29 countries. These institutions reported having conducted 429 trials, leading to 332 publications, of which 43% were first and 44% were last authorships by those institutions. For future trials, 98% of respondents (93/95) said they would be interested in sharing data, although only 34% had shared data already (23/68, p < 0.001). The major barriers to data sharing were data protection (78%, 74/95), ethical issues (49%, 47/95), and the lack of a data sharing platform (49%, 47/95). Of the respondents, 89% believed a platform would facilitate data sharing (85/95 vs. 10/95 did not, p < 0.001) and should offer easy data uploading (74%, 70/95), data safety (66%, 63/95), easy communication between providers and re-users (62%, 59/95), and data access policies (56%, 53/95). CONCLUSION: A considerable number of imaging trials are being performed and published by radiologists in Europe whilst data sharing is hardly taking place, despite great interest. This is most likely due to data protection and ethical issues, as well as the absence of a data sharing platform. KEY POINTS: • Radiologists have performed a considerable number of more than 400 imaging trials in the last 5 years. • Although only 34% of institutions had shared trial data already, 98% are interested in doing so. • Major data sharing barriers are ethics, data protection, and the absence of a sharing platform.

Age and Computed Tomography and Invasive Coronary Angiography in Stable Chest Pain: A Prespecified Secondary Analysis of the DISCHARGE Randomized Clinical Trial.

Importance: The effectiveness and safety of computed tomography (CT) and invasive coronary angiography (ICA) in different age groups is unknown. Objective: To determine the association of age with outcomes of CT and ICA in patients with stable chest pain. Design, Setting, and Participants: The assessor-blinded Diagnostic Imaging Strategies for Patients With Stable Chest Pain and Intermediate Risk of Coronary Artery Disease (DISCHARGE) randomized clinical trial was conducted between October 2015 and April 2019 in 26 European centers. Patients referred for ICA with stable chest pain and an intermediate probability of obstructive coronary artery disease were analyzed in an intention-to-treat analysis. Data were analyzed from July 2022 to January 2023. Interventions: Patients were randomly assigned to a CT-first strategy or a direct-to-ICA strategy. Main Outcomes and Measures: MACE (ie, cardiovascular death, nonfatal myocardial infarction, or stroke) and major procedure-related complications. The primary prespecified outcome of this secondary analysis of age was major adverse cardiovascular events (MACE) at a median follow-up of 3.5 years. Results: Among 3561 patients (mean [SD] age, 60.1 [10.1] years; 2002 female [56.2%]), 2360 (66.3%) were younger than 65 years, 982 (27.6%) were between ages 65 to 75 years, and 219 (6.1%) were older than 75 years. The primary outcome was MACE at a median (IQR) follow-up of 3.5 (2.9-4.2) years for 3523 patients (99%). Modeling age as a continuous variable, age, and randomization group were not associated with MACE (hazard ratio, 1.02; 95% CI, 0.98-1.07; P for interaction = .31). Age and randomization group were associated with major procedure-related complications (odds ratio, 1.15; 95% CI, 1.05-1.27; P for interaction = .005), which were lower in younger patients. Conclusions and Relevance: Age did not modify the effect of randomization group on the primary outcome of MACE but did modify the effect on major procedure-related complications. Results suggest that CT was associated with a lower risk of major procedure-related complications in younger patients. Trial Registration: ClinicalTrials.gov Identifier: NCT02400229.

Modulation of direct electron transfer of cytochrome c by use of a molecularly imprinted thin film.

We describe the preparation of a molecularly imprinted polymer film (MIP) on top of a self-assembled monolayer (SAM) of mercaptoundecanoic acid (MUA) on gold, where the template cytochrome c (cyt c) participates in direct electron transfer (DET) with the underlying electrode. To enable DET, a non-conductive polymer film is electrodeposited from an aqueous solution of scopoletin and cyt c on to the surface of a gold electrode previously modified with MUA. The electroactive surface concentration of cyt c was 0.5 pmol cm(-2). In the absence of the MUA layer, no cyt c DET was observed and the pseudo-peroxidatic activity of the scopoletin-entrapped protein, assessed via oxidation of Ampliflu red in the presence of hydrogen peroxide, was only 30% of that for the MIP on MUA. This result indicates that electrostatic adsorption of cyt c by the MUA-SAM substantially increases the surface concentration of cyt c during the electrodeposition step, and is a prerequisite for the productive orientation required for DET. After template removal by treatment with sulfuric acid, rebinding of cyt c to the MUA-MIP-modified electrode occurred with an affinity constant of 100,000 mol(-1) L, a value three times higher than that determined by use of fluorescence titration for the interaction between scopoletin and cyt c in solution. The DET of cyt c in the presence of myoglobin, lysozyme, and bovine serum albumin (BSA) reveals that the MIP layer suppresses the effect of competing proteins.

Comparative effectiveness of initial computed tomography and invasive coronary angiography in women and men with stable chest pain and suspected coronary artery disease: multicentre randomised trial.

OBJECTIVE: To assess the comparative effectiveness of computed tomography and invasive coronary angiography in women and men with stable chest pain suspected to be caused by coronary artery disease. DESIGN: Prospective, multicentre, randomised pragmatic trial. SETTING: Hospitals at 26 sites in 16 European countries. PARTICIPANTS: 2002 (56.2%) women and 1559 (43.8%) men (total of 3561 patients) with suspected coronary artery disease referred for invasive coronary angiography on the basis of stable chest pain and a pre-test probability of obstructive coronary artery disease of 10-60%. INTERVENTION: Both women and men were randomised 1:1 (with stratification by gender and centre) to a strategy of either computed tomography or invasive coronary angiography as the initial diagnostic test (1019 and 983 women, and 789 and 770 men, respectively), and an intention-to-treat analysis was performed. Randomised allocation could not be blinded, but outcomes were assessed by investigators blinded to randomisation group. MAIN OUTCOME MEASURES: The primary endpoint was major adverse cardiovascular events (MACE; cardiovascular death, non-fatal myocardial infarction, or non-fatal stroke). Key secondary endpoints were an expanded MACE composite (cardiovascular death, non-fatal myocardial infarction, non-fatal stroke, transient ischaemic attack, or major procedure related complication) and major procedure related complications. RESULTS: Follow-up at a median of 3.5 years was available in 98.9% (1979/2002) of women and in 99.0% (1544/1559) of men. No statistically significant gender interaction was found for MACE (P=0.29), the expanded MACE composite (P=0.45), or major procedure related complications (P=0.11). In both genders, the rate of MACE did not differ between the computed tomography and invasive coronary angiography groups. In men, the expanded MACE composite endpoint occurred less frequently in the computed tomography group than in the invasive coronary angiography group (22 (2.8%) v 41 (5.3%); hazard ratio 0.52, 95% confidence interval 0.31 to 0.87). In women, the risk of having a major procedure related complication was lower in the computed tomography group than in the invasive coronary angiography group (3 (0.3%) v 21 (2.1%); hazard ratio 0.14, 0.04 to 0.46). CONCLUSION: This study found no evidence for a difference between women and men in the benefit of using computed tomography rather than invasive coronary angiography as the initial diagnostic test for the management of stable chest pain in patients with an intermediate pre-test probability of coronary artery disease. An initial computed tomography scan was associated with fewer major procedure related complications in women and a lower frequency of the expanded MACE composite in men. TRIAL REGISTRATION: NCT02400229ClinicalTrials.gov NCT02400229.

Microelectrospotting as a new method for electrosynthesis of surface-imprinted polymer microarrays for protein recognition.

Here we introduce microelectrospotting as a new approach for preparation of protein-selective molecularly imprinted polymer microarrays on bare gold SPR imaging chips. During electrospotting both the gold chip and the spotting tip are electrically connected to a potentiostat as working and counter electrodes, respectively. The spotting pin encloses the monomer-template protein cocktail that upon contacting the gold surface is in-situ electropolymerized resulting in surface confined polymer spots of ca. 500 µm diameter. By repeating this procedure at preprogrammed locations for various composition monomer-template mixtures microarrays of nanometer-thin surface-imprinted films are generated in a controlled manner. We show that the removal and rebinding kinetics of the template and various potential interferents to such microarrays can be monitored in real-time and multiplexed manner by SPR imaging. The proof of principle for microelectrospotting of electrically insulating surface-imprinted films is made by using scopoletin as monomer and ferritin as protein template. It is shown that microelectrospotting in combination with SPR imaging can offer a versatile platform for label-free and enhanced throughput optimization of the molecularly imprinted polymers for protein recognition and for their analytical application.

Peroxide-dependent analyte conversion by the heme prosthetic group, the heme Peptide "microperoxidase-11" and cytochrome C on chitosan capped gold nanoparticles modified electrodes.

In view of the role ascribed to the peroxidatic activity of degradation products of cytochrome c (cyt c) in the processes of apoptosis, we investigate the catalytic potential of heme and of the cyt c derived heme peptide MP-11 to catalyse the cathodic reduction of hydrogen peroxide and to oxidize aromatic compounds. In order to check whether cyt c has an enzymatic activity in the native state where the protein matrix should suppress the inherent peroxidatic activity of its heme prosthetic group, we applied a biocompatible immobilization matrix and very low concentrations of the co-substrate H2O2. The biocatalysts were entrapped on the surface of a glassy carbon electrode in a biocompatible chitosan layer which contained gold nanoparticles. The electrochemical signal for the peroxide reduction is generated by the redox conversion of the heme group, whilst a reaction product of the substrate oxidation is cathodically reduced in the substrate indication. The catalytic efficiency of microperoxidase-11 is sufficient for sensors indicating HRP substrates, e.g., p-aminophenol, paracetamol and catechol, but also the hydroxylation of aniline and dehalogenation of 4-fluoroaniline. The lower limit of detection for p-aminophenol is comparable to previously published papers with different enzyme systems. The peroxidatic activity of cyt c immobilized in the chitosan layer for catechol was found to be below 1 per mill and for p-aminophenol about 3% as compared with that of heme or MP-11.